Comparative Effects of a D2 and Mixed D1-D2 Dopamine Antagonist on Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Subjective Reinforcement Self-report Scales
研究概览
简要总结
To determine if:
- pathological gambling is similar to psychostimulant addiction as reflected by parallel roles for D1 and D2 receptors in gambling and stimulant reinforcement.
- these parallel roles are linked with gambling pathology or if they are evident in both gamblers and controls.
详细描述
BACKGROUND: No previous research appears to have investigated the role of dopamine (DA) D1 or D2 receptors in psychostimulant reinforcement in pathological gamblers. Effects of haloperidol vs. placebo will reveal the role of D2 and the effects of fluphenazine vs. haloperidol will reveal the role of D1 in this process.
OBJECTIVE: This study will begin to define the neurochemistry of Pathological Gambling by examining the roles of dopamine D1 and D2 receptors in gambling reinforcement and psychostimulant reinforcement, and exploring genetic predictors of response to DA probes in Pathological Gambling subjects (subjects) and healthy controls.
METHODS: A double-blind, placebo controlled, counterbalanced between-within design will be employed. Each participant will attend 4 sessions with a minimum of 1 week between sessions to ensure drug washout. Responses to the slot machine will be assessed in sessions 1 and 2 (Phase I), and responses to amphetamine will be assessed in sessions 3 and 4 (Phase II). A second capsule (dummy) will be administered at expected peak levels for each antagonist on sessions 1 and 2 to standardize the procedure across sessions.
Subjective reinforcement self-report scales will be administered at key intervals throughout the study.
HYPOTHESIS: It is hypothesized that haloperidol (3-mg) will increase priming (Desire to Gamble, Gambling word salience) and pleasurable effects (e.g., Enjoyment/Liking) induced by playing a slot machine in Pathological Gambling subjects (N = 40). If gambling and stimulant reinforcement are mediated by common mechanisms, haloperidol will also increase priming and pleasurable effects of amphetamine (20-mg) in Pathological Gambling subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PATHOLOGICAL GAMBLERS
- •otherwise healthy, non-treatment seeking, non-abstinent
- •male or female
- •ages 19-65
- •DSM-IV PG symptom scale score > 5
- •SOGS (South Oaks Gambling Screen) score > 5
- •nicotine dependence acceptable
- •male or female
- •ages 19-65
- •DSM-IV PG symptom scale score = 0
- •SOGS score = 0
- •nicotine dependence acceptable
- •must have played slot machine > 5 times
排除标准
- •both Pathological Gamblers and Controls
- •Axis I psychopathology aside from nicotine dependence (or PG) based on SCID
- •Schizotypal or Borderline Personality Disorder based on psychiatric interview
- •Family history of schizophrenia or bipolar disorder
- •English comprehension below grade 7 level.
- •ADS (Alcohol Dependence Scale) > 13 (more than low dependence)
- •BDI (Beck Depression Inventory) short form > 10 (more than low depression)
- •DAST (Drug Abuse Screening Test) > 4 (possible drug abuse)
- •Consumption of > 20/15 (men/women) standard alcoholic drinks/ week (hazardous drinking)
- •Smoking > 20 cigarettes/day to help minimize withdrawal symptoms during test phase
- •Any prior use of psychostimulant drugs
- •Current use of medication that could interact with any of the study medications
- •Women who are pregnant or breastfeeding
研究组 & 干预措施
Haloperidol
Subjects randomized to pre-treatment drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Haloperidol (Drug)
Haloperidol
Subjects randomized to pre-treatment drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Dexedrine (Drug)
Haloperidol
Subjects randomized to pre-treatment drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Placebo (Drug)
Haloperidol
Subjects randomized to pre-treatment drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Slot Machine (Behavioral)
Fluphenazine
Subjects randomized to pre-treatment drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Fluphenazine (Drug)
Fluphenazine
Subjects randomized to pre-treatment drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Dexedrine (Drug)
Fluphenazine
Subjects randomized to pre-treatment drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Placebo (Drug)
Fluphenazine
Subjects randomized to pre-treatment drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).
Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules
Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.
Response measured to 15 min session of a commercial slot machine game.
干预措施: Slot Machine (Behavioral)
结局指标
主要结局
Subjective Reinforcement Self-report Scales
时间窗: At key points in testing: immediately after the slot machine game, and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration).
Self-reported Confidence to Refrain from Gambling (0 - 10) was assessed at test session baseline, before the slot machine and after the slot machine (Phase 1); and before amphetamine and at peak amphetamine (Phase 2). The maximum score (10) denotes complete confidence to refrain from gambling (i.e., NO urge or compulsion to gamble); the minimum score (0) denotes complete lack of confidence to refrain from gambling (i.e., overwhelming urge to gamble). Scores between 10 and 0 denote intermediate confidence to refrain from gambling with LOWER scores denoting less confidence to refrain from gambling -- i.e., GREATER urge or compulsive motivation to gamble. Scores shown are based on single item visual analogue ratings 0-10 from each participant at the specified time point. The mean (SD) of these single item ratings is presented for each sub-group.
次要结局
- Betting Behaviour in Laboratory-based Slot Machine Game(1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week))
- Speed of Play on Slot Machine Game(15-minutes)
- Winnings on Slot Machine Upon Completion of Game(15-minutes)
- Diastolic Blood Pressure (DBP)(At key points in testing: immediately after the slot machine game (change from session baseline), and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)(change from session baseline).)
- Cognitive Task Performance(At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration))
研究者
Daniela Lobo
Clinician Scientist
Centre for Addiction and Mental Health